title: Polynitroxylated-pegylated hemoglobin attenuates fluid requirements and brain edema in combined traumatic brain injury plus hemorrhagic shock in mice.
abstract: Polynitroxylated-pegylated hemoglobin (PNPH), a bovine hemoglobin decorated with nitroxide and polyethylene glycol moieties, showed neuroprotection vs. lactated Ringer's (LR) in experimental traumatic brain injury plus hemorrhagic shock (TBI+HS).
  
  
  OBJECTIVE
  Resuscitation with PNPH will reduce intracranial pressure (ICP) and brain edema and improve cerebral perfusion pressure (CPP) vs. LR in experimental TBI+HS. C57/BL6 mice (n=20) underwent controlled cortical impact followed by severe HS to mean arterial pressure (MAP) of 25 to 27 mm Hg for 35 minutes. Mice (n=10/group) were then resuscitated with a 20 mL/kg bolus of 4% PNPH or LR followed by 10 mL/kg boluses targeting MAP>70 mm Hg for 90 minutes. Shed blood was then reinfused. Intracranial pressure was monitored. Mice were killed and %brain water (%BW) was measured (wet/dry weight). Mice resuscitated with PNPH vs. LR required less fluid (26.0±0.0 vs. 167.0±10.7 mL/kg, P<0.001) and had a higher MAP (79.4±0.40 vs. 59.7±0.83 mm Hg, P<0.001). The PNPH-treated mice required only 20 mL/kg while LR-resuscitated mice required multiple boluses. The PNPH-treated mice had a lower peak ICP (14.5±0.97 vs. 19.7±1.12 mm Hg, P=0.002), higher CPP during resuscitation (69.2±0.46 vs. 45.5±0.68 mm Hg, P<0.001), and lower %BW vs. LR (80.3±0.12 vs. 80.9±0.12%, P=0.003). After TBI+HS, resuscitation with PNPH lowers fluid requirements, improves ICP and CPP, and reduces brain edema vs. LR, supporting its development.
authors.affiliation: Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA.
authors.forename: Erik C
authors.initials: EC
authors.lastname: Brockman
authors.forename: Hülya
authors.initials: H
authors.lastname: Bayır
authors.forename: Brian
authors.initials: B
authors.lastname: Blasiole
authors.forename: Steven L
authors.initials: SL
authors.lastname: Shein
authors.forename: Ericka L
authors.initials: EL
authors.lastname: Fink
authors.forename: Cedward
authors.initials: C
authors.lastname: Dixon
authors.forename: Robert S B
authors.initials: RS
authors.lastname: Clark
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Vagni
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Carleton J C
authors.initials: CJ
authors.lastname: Hsia
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Tisherman
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology*; D001929:Brain Edema / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002417:Cattle; D006454:Hemoglobins / Q000494:pharmacology*; D007427:Intracranial Pressure / Q000187:drug effects; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D018696:Neuroprotective Agents; C121926:polynitroxyl hemoglobin